Modified antibodies and related compounds, compositions and methods of use

Abstract

Provided herein are modified antibodies, compounds used to make them, and intermediates in their synthesis; compositions; formulations and methods, including methods of treating diseases, disorders or conditions, for example, cancer, in humans.

What is claimed is: 
     
       1. A modified antibody represented by the following formula (IIa): 
       
         
           
           
               
               
           
         
         wherein:
 A is an antibody or antibody fragment; 
 the two depicted cysteine residues are from at least one reduced interchain cysteine-cysteine disulfide bond in A; 
 n is an integer from 1 to 13; 
 the   bond represents a single or a double bond; and 
 each R and R′ is independently hydrogen or C 1-6  alkyl, wherein one or more carbons in the C 1-6  alkyl are optionally substituted by a group selected from an oxo, a thio, an imine, and a substituted imine. 
 
       
     
     
       2. The modified antibody of  claim 1 , wherein the modified antibody is represented by the following formula (IId): 
       
         
           
           
               
               
           
         
         wherein:
 each R a  and R a ′ is independently hydrogen, C 1-3 alkyl, or absent. 
 
       
     
     
       3. The modified antibody of  claim 1 , wherein the   bond represents a single bond. 
     
     
       4. The modified antibody of  claim 1 , wherein n is 4. 
     
     
       5. The modified antibody of  claim 1 , wherein A is an antibody that is specific to a cancer antigen. 
     
     
       6. The modified antibody of  claim 1 , wherein A is selected from the group consisting of alemtuzumab, anitumumab, bevacizumab, brentuximab, cetuximab, gemtuzumab, glembatumumab, inotuzumab, ipilimumab, lovortumumab, milatuzumab, ofatumumab, rituximab, tositumomab, and trastuzumab.